Imaging in Coronary Artery Disease

Updated: Sep 29, 2016
  • Author: Justin D Pearlman, MD, ME, PhD, FACC, MA; Chief Editor: Eugene C Lin, MD  more...
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Overview

Overview

Coronary artery disease (CAD) is a complex disease that causes reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. The disease may be focal or diffuse. Apart from rare congenital anomalies (birth defects), coronary artery disease is usually a degenerative disease, uncommon as a clinical problem before the age of 30 years and common by the age of 60 years. One in four people will have a heart attack. The first recognized symptom may be death. The term coronary is derived from crown, referring to the way these arteries sit on the heart.

The American College of Radiology notes that coronary artery disease has a long asymptomatic latent period and that early targeted preventive measures can reduce mortality and morbidity. Imaging modalities for evaluating patients at increased risk for CAD include radiography, fluoroscopy, multidetector CT, ultrasound, MRI, cardiac perfusion scintigraphy, echocardiography, and positron emission tomography (PET). [1]

See the images below depicting the coronary arteries and CAD.

Selective injection image of the left coronary art Selective injection image of the left coronary arteries. D1 = first diagonal, LAD = left anterior descending artery, LCX = left circumflex, LM = left main coronary artery, and OM1= first obtuse marginal.
Contrast-labeled blood to the heart is used to ide Contrast-labeled blood to the heart is used to identify the territory at risk. The results of this assessment of the delayed arrival compares favorably to the findings of radionuclide stress imaging, and stress induction of ischemia is not required to identify the zone at risk.
Compared with radionuclide images of blood deliver Compared with radionuclide images of blood delivery, MRIs and CT scans improve resolution, depiction of the functional effect and the relationship to the coronary supply, and identification of the area at risk without stress. The advantage of radionuclide imaging is primarily its predictive value; stress echocardiography has similar predictive value. MRI and CT have been less available than other studies; therefore, data on their value are relatively limited.

Stable and unstable lesions

Lesions that cause blockages in the coronary arteries may be stable or unstable. Unstable lesions activate blood clotting and/or vascular spasm. Indications that CAD may be unstable include recent onset or familiar symptoms that are increasing in frequency, in duration, or in severity or with decreasing exertion tolerance or at rest. The term "chest pain" is a code phrase — the symptoms of CAD do not have to be in the chest and do not have to include pain. I prefer the phrase "heart warning" symptoms. When a warning light is activated, you should resolve the problem quickly even if it is low in intensity.

Unstable symptoms of CAD may represent a threatened heart attack. After as little as 5 minutes, a wall of the heart may stop functioning but still be salvageable — that is called stun. After as little as 10-20 minutes permanent damage may accumulate, summarized by the phrase "time is muscle." If the symptoms are new or if they are familiar but unstable or are not reliably fully resolved in 5 minutes, emergency help is recommended because "time is muscle." Intervention completed within 60 minutes improves outcome. The symptoms of a threatened heart attack may be very mild.

Ischemia

When the heart has inadequate blood supply (ie, ischemia), pressure may be felt in the chest that moves to the left arm; one may feel weak, sweaty, or short of breath or nauseated; palpitations (ie, change in heart rhythm) may occur; or there may be a sensation of pressure or tightness just in the chest, neck, or arms.

Many patients mistake the heart warning symptoms for heartburn or gas. If symptoms occur that may represent inadequate blood supply to the heart, one should rest immediately and take nitroglycerin, if available. If symptoms last more than 5 minutes, occur at rest, or keep coming back, one should call 911, chew a full-sized aspirin (325 mg) if not allergic, and continue taking nitroglycerin every 5 minutes as long as it does not cause dizziness or light-headedness.

For excellent patient education resources, see eMedicineHealth's Cholesterol Center. Also, visit eMedicineHealth's patient education articles Chest Pain, Coronary Heart Disease, and Heart Attack.

Severity of CAD

The severity of CAD is defined several ways, including the following:

  • Anatomically, by visualizing the blood vessel branches and any blockages to blood flow along the pathways
  • Functionally, by estimating blood delivery to tissue supplied by each branch vessel
  • Clinically, by determining what symptoms correspond to inadequate blood delivery, what level of activity causes them, what relieves them, and the pattern of occurrences

Such patterns are described as unstable if the pattern includes variable or accelerating frequency, variable or increasing severity or changing character of symptoms, or variable or decreasing exercise threshold or if symptoms continue or recur just after a heart attack.

In addition, one examines the consequences, including the location and extent of reversible and of permanent impairment, motion and thickening of affected segments of the heart, and whether the damage is causing or sustaining life-threatening arrhythmias.

One also evaluates the patient's overall cardiac performance, which is typically expressed as the ejection fraction (EF), or percentage of the contents the left ventricle pumps forward in a heartbeat, and exertion tolerance, graded 1-4 (1=normal, 4=bedridden).

The TIMI (Thrombolysis in Myocardial Infarction) risk score looks at 7 factors that point to bad outcomes:

  1. Age 65 years or older
  2. At least 3 risk factors for coronary artery disease
  3. Prior coronary stenosis of 50% or more
  4. ST-segment deviation on electrocardiogram at presentation greater than 0.5 mm
  5. At least 2 anginal events in prior 24 hours
  6. Use of aspirin in prior 7 days
  7. Elevated serum cardiac markers

TIMI risk scores have the following risk of all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization within the first 2 weeks: 1=5%, 2=8%, 3=13%, 4=20%, 5=26%, 6/7=41%. [2]

Imaging of CAD

At present, achieving the best resolution on images of the coronary arteries requires catheterization, injection of an iodinated contrast agent, and use of a radiographic technique. As an alternative, multidetector-row CT (MDCT) or MRI may be used to clarify coronary anatomy and to determine whether a vessel is occluded.

Stress imaging has a complementary role in depicting zones with inducible ischemia (blood supply inadequate for the demands of the tissue). Stress may be produced with exercise, an infusion of a medication that increases the strength of cardiac contractions (eg, dobutamine), or an infusion of a medication (eg, adenosine, dipyridamole) that dilates the vessels and thereby reduces the delivery of blood to diseased branches.

More than a decade ago, MRI was shown to be capable of imaging the coronary arteries and demonstrating stenoses without catheterization or injection of contrast material. [3] MDCT is now proving to be a fast and useful alternative for defining the coronary anatomy. [4] MRI takes more time than MDCT and generally provides less detail of the coronary anatomy, but it avoids ionizing radiation and the use of iodinated contrast agent.

Advances in MRI and CT have markedly improved the speed and resolution of imaging, making these modalities useful in the clinical evaluation of CAD while improving their safety and convenience. In addition to defining the anatomy, both MRI and CT can be used to identify zones of impaired blood supply by timing of the arrival of contrast agent–labeled blood.

In addition, MRI is useful in identifying the location and thickness of myocardial scars. Although neither MRI nor CT has replaced coronary angiography (XRA) as the clinical standard for the diagnosis of coronary stenosis, their use in determining if a vessel is open is increasing. Recently, 64-slice multidetector-row CT angiography (CTA) has shown potential as an alternative to coronary angiography for the identification of coronary blockages. [5] In a study of 15,207 intermediate likelihood patients without known CAD, the severity of CAD on coronary CTA was predictive of the need for invasive coronary artery catheterization or revascularization. This suggests that coronary CTA may be an effective gatekeeper for invasive catheterization. [6]

Assessment of tissue viability

The amount of impairment or damage caused by stenosis obstructing a coronary artery depends on how much of the myocardium the vessel supplies, the severity of the stenosis and any superimposed spasm, the level of demand in the tissue it supplies, and the condition of the tissue it supplies.

When demand exceeds supply, the tissue becomes ischemic, which means blood supply is insufficient to maintain normal metabolism. Myocardial ischemia may cause chest pain, fatigue, shortness of breath, or another form of reduced exertion tolerance.

Ischemia may have no symptoms but may be detected as impaired blood delivery, impaired contractile function (wall motion or wall-thickening abnormality on dynamic cardiac imaging series), or interference with the movement of ions (resulting in depolarization and repolarization abnormalities on ECGs as ST-segment shifts, changes in ST and T waves, and/or rhythm abnormalities); and/or it may be detected when a blood test shows a release of enzymes (creatine kinase-MB [CK-MB], troponin-I, troponin-T) from the heart muscle.

Ischemia may deplete high-energy phosphate carriers (eg, creatine, adenosine) that are needed for muscle contraction. Depletion may occur to the point that impaired motion may persist even when ischemia is relieved. Transiently impaired contractile function of muscle that persists after the relief from ischemia is called stun, and long-term dysfunction of viable muscle is called hibernation.

Dead tissue converted to scar likewise loses contractile function. Therefore, a key issue when a region of heart wall shows loss of function is the determination of whether the myocardium is still viable. Persistent wall-motion abnormality at rest shown by imaging (echocardiography, MRI, CT, coronary angiography) can raise the issue of tissue viability and, in particular, whether repairing a blockage in the blood supply is likely to be beneficial.

If a region is thin and akinetic (no motion), it is more likely to scar (dead myocardium) than if it is not. However, when in doubt, viability tests are appropriate. For example, viability can be identified by performing phosphorus-31 MRI and by reporting for each region the relative concentrations of creatine phosphate; inorganic phosphate; and adenosine monophosphate, diphosphate, and triphosphate.

Although MRI of phosphorylated metabolites and positron emission tomography (PET) of metabolic activity (to assess glucose utilization) can be used to assess tissue viability, an alternative method of equal, if not better, clinical value is imaging by MRI with contrast to identify contrast retention by damaged myocardium. We first observed that phenomenon over a decade ago when studying an animal model of ischemia and infarction while looking at angiogenesis (treatments to promote development of the blood supply).

Another way to identify viability is to examine wall motion at rest and with light stress. Dobutamine stress imaging may be performed with MRI or echocardiography. Dobutamine stress tests are used to detect viability by demonstrating dose-related increases in contractility if the tissue is viable. An increase in the dose of dobutamine may subsequently elicit a decline in contractility associated with induced ischemia—that is, a biphasic response, indicating viable but threatened myocardium.

Early in the development of perfusion imaging [7, 8] , we observed retention of gadolinium contrast by injured myocardium. Normally, a bolus of contrast agent washes out of the heart walls within 5-10 minutes. Any contrast agent seen in the heart after the agent has washed out of normal zones demarcates injured myocardium.

This technique has since been called MRI scar mapping or delayed enhancement imaging. The fraction of wall thickness that retains gadolinium-based contrast agent 10-20 minutes after a bolus infusion of 20 mL/75 kg indicates viability. The result is an excellent predictor of potential for functional recovery. If the scar is less than one third the thickness of the wall, improvement with revascularization is likely. However, if the scar is more than two thirds the thickness of the wall, improvement after revascularization is unlikely.

MRI scar maps depict contrast retention due to cell disruption. Although acute injury results in slightly enlarged zones of retained contrast agent on MRI, after a week, the defined zone appears the same months to years later and it corresponds on pathology to dead tissue.

Unfortunately, in patients with poor renal function, gadolinium contrast may stay in the body long enough to cause a potentially disabling inflammatory reaction called nephrogenic systemic sclerosis, also known as nephrogenic fibrosing dermopathy (NSF/NFD).

NSF/NFD has been linked to all the gadolinium-based contrast agents. For more information, see Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

Appropriate and timely treatment

When symptoms suggestive of a possible threatened heart attack are present (persisting chest pain or pressure radiating to 1 or both arms or jaw; or unexplained shortness of breath, weakness, sudden sweating, or a serious arrhythmia), an electrocardiogram should be obtained promptly, with continual monitoring for arrhythmia or ischemia (impaired blood supply).

Ambulances have both ECG and rhythm and oxygenation monitoring equipment, as do emergency departments. The ECG can show ST segment shifts and/or T-wave inversions as signs of heart ischemia or injury. However, there are electrically silent areas in the standard monitors. A 12-lead ECG does not detect all of the electrical warning signs of heart damage; more extensive thoracic coverage is desirable.

Preferred examination

If a patient has symptoms, suggestive ECG findings, or imaging results that indicate a need for intervention, coronary angiography by means of catheterization is currently the preferred examination for identifying the culprit lesions and, often, for providing an interventional remedy during a single session.

The patient's clinical history (age, symptoms, risk factors) provides an estimate of disease likelihood. The basic screening test is stress ECG, which can adjust prognosis depending on the pretest likelihood of disease.

Generally, if the patient has no symptoms and the resting and stress ECGs are normal, the risk of mortality in the next year is low. However, the predictive accuracy of ECG even at peak stress as part of stress testing overall is not good, with as much as one half of all cases of disease missed by ECG. The simple addition of stress testing of B-type natriuretic peptide (BNP) levels in the blood markedly improves the predictive accuracy. [9] Other ways to improve accuracy are nuclear imaging, echocardiography, MRI, or CT.

Stress nuclear imaging is widely used to assess the patient's exercise tolerance and to identify zones of inducible ischemia (jeopardized myocardium), which is useful information, even after coronary angiography is performed. PET offers similar rest-stress data and is superior for identifying viable myocardium. Jeopardy and viability are important issues, because if the myocardium is not at risk or if it is not viable, revascularization (bypass or angioplasty) will not help that part of the heart.

Echocardiography to identify wall motion abnormalities has a similar predictive accuracy in patients with intermediate suspicion of CAD, estimated at 80-90%. Echocardiography avoids radiation exposure, which may cause as much as 1 new cancer for every thousand patients studied, but radionuclide imaging (thallium, sestamibi) is preferred if the patient already has old wall motion abnormalities or has poor echo windows (lung blocks the views).

Exercise stress echo may be performed before and after treadmill exercise or during exercise on a supine bicycle. The latter requires more cooperation but allows imaging at every stage, so it may avoid false negatives from rapid recovery or from involvement of all areas (balanced ischemia).

MRI and CT have markedly improved the ability to depict zones of impaired blood supply and to display the coronary anatomy. MRI and CT do not require stress; they offer sensitivity and specificity similar to those of nuclear imaging; they achieve resolution better than that of nuclear imaging; and they can demonstrate the 3-dimensional (3D) coronary anatomy. [10] Therefore, MRI and CT complement the combination of stress test and catheterization, and in some settings, MRI and/or CT may replace them (eg, by demonstrating normal results).

EBT offers similar value. EBT is a form of CT in which an electron beam, rather than the entire x-ray source, is rotated around the patient. Also, EBT and CT have been used as a screening test to screen for calcifications in the coronary arteries as a marker for risk of coronary disease in young patients.

To monitor angiogenesis, collateral-sensitive and delayed-arrival MRI appear to be far more sensitive than any other technique. Collateral-sensitive MRI generates a dark flare of susceptibility effect due to sparse neovascular development at an early stage while suppressing a similar effect from the LV. This finding is a strong predictor (r = 0.93) of improved blood delivery.

Data from quantitative studies of the extent of delayed arrival in humans and from double-blind postmortem evaluations in porcine models of chronic myocardial ischemia and angiogenesis have validated this method. [7] This finding clearly distinguishes angiogenic treatment from control at 4 weeks after treatment, and the benefit is followed by improvements in wall motion (serial motion assessment by reference tracking [SMART] measurements). [11]

Limitations of techniques

Coronary angiography is considered the criterion standard for evaluating coronary artery stenosis. Flow limitations may be estimated by using the TIMI (Thrombolysis in Myocardial Infarction)score and confirmed by using a flow wire or by performing IVUS. [12] If coronary angiography fails to depict a culprit lesion and if cardiac ischemia is inducible, the patient may have syndrome X (microvascular disease).

Coronary angiography requires the use of iodine, which may cause serious allergic reactions, including anaphylaxis and also renal failure. Use of large volumes of saline and the antioxidant acetylcysteine may help prevent renal failure. The catheterization procedure can induce vessel spasm and/or tear the lining of a vessel, resulting in occlusion and, possibly, death in a patient who may not have had coronary artery disease (CAD). The procedure can also result in embolism, which may cause stroke or limb loss. Nerve damage, infection, and other complications are possible as well. The death rate is approximately 0.1%.

Nuclear imaging produces low-resolution images that may depict an apparent defect resulting from breast tissue, hiccups, paradoxical septal motion, or other confounding factors. Nuclear imaging may fail to depict disease because of submaximal stress. Tomographic imaging, attenuation correction, or PET substantively eliminate the problems resulting from breast attenuation. The newer combinations of nuclear imaging with CT enable the most accurate correction of nuclear event maps for attenuation by overlying tissues.

MRI requires special precautions in patients with pacemakers or recently placed aneurysm clip. Patients with claustrophobia require premedication, mirrors, and/or an open magnet. Many magnets do not accommodate patients who weigh more than 300 lb. Arrhythmias commonly lower image quality.

CT contrast agents usually contain iodine, which may cause an allergic reaction and possibly anaphylaxis. Nonionic contrast material reduces the risk of harm, as does pretreatment with steroids. Gadopentetate dimeglumine, the contrast agent used for MRI, may be used for CT if patients are allergic to iodine-based media.

CT uses x-rays typically equivalent to the dose needed for about 200 chest radiographs. A single routine CT study in a child increases the lifetime risk of cancer by 0.35% per scan. [13] In adults, the lifetime risk of cancer may be as high as 2% with annual CT screening. Because the breast has high radiosensitivity, techniques to reduce tissue exposure, such as displacing the breasts outside the direct x-ray beam and using a lead shield, can reduce radiation hazard of CTA. [14]

According to the 2015 update of the European procedural guidelines for radionuclide myocardial perfusion imaging (MPI) with SPECT, absolute contraindications for iodine contrast include myasthenia gravis, mastocytosis, and post-thyroid carcinoma when follow-up with 131I imaging or 131I therapy is planned within 6 months of CT angiography. [15]

Risk factors that may warrant preadministration serum creatinine screening in patients who are scheduled to receive intravascular iodinated contrast medium include the following [15] :

  • Age >60 yr
  • History of renal disease, including dialysis, kidney transplant, single kidney, renal cancer, renal surgery
  • History of hypertension requiring medical therapy
  • Diabetes mellitus

The use of contrast media for cardiac imaging is increasing as hybrid cardiac SPECT/CT and PET/CT, as well as coronary CT angiography and cardiac MRI, become more widely used.  Hybrid imaging provides a noninvasive assessment of coronary anatomy and myocardial perfusion. [16, 15]

Imaging guidance of interventional procedures

Coronary angiography is widely used to guide interventions, such as balloon angioplasty, atherectomy, laser treatment, stent placement, and other procedures. Current practice indicates the use of coronary angiography in patients with potentially treatable lesions to confirm the findings and to perform interventions. Both tasks may be accomplished in a single procedure.

Cardiac catheterization is recommended for patients with mild angina (class I or II) plus an EF of less than 45%, including patients with noninvasive test results indicating a high risk, those with an uncertain diagnosis after noninvasive testing, patients with serious ventricular arrhythmias, and those who survive an episode of sudden death. The only indication with submaximal support is mild angina with reduced EF; this is a class IIa recommendation. The classification of indications by the American College of Cardiology indicates the weight of evidence in support of the recommendation. Mild angina with no reduction in EF might be managed with medication as a therapeutic trial.

As an experiment, MRI, CT, or echocardiography may be used to guide interventional procedures. MRI does not involve ionizing radiation; therefore, imaging may be active throughout the procedure. However, special guidewires and other equipment compatible with the magnet and the rapidly changing magnetic field must be used, and staff must be trained to ensure that no magnetic objects are brought near the magnet.

CT uses ionizing radiation and is slower than coronary angiography, but it provides 3D information that may facilitate localization, especially for newer interventions such as the intramyocardial injection of angiogenic growth factors or stem cells. 3D ultrasonography similarly facilitates accurate injections, with convenience of portability and without a need for lead shielding from x-rays.

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Radiography

Coronary angiography shows where vessels originate, how they branch, whether they have obstructions or dissections or thrombi, the degree of any obstructions, and which territories they supply. See the x-ray angiograph below.

X-ray angiography is the criterion standard for de X-ray angiography is the criterion standard for delineating the coronary anatomy, but it is inferior to MRI and CT in identifying myocardium with impaired blood delivery, in assessing the functional consequences, and in identifying the development of microvascular collaterals.

Some key questions answered during an examination of the anatomy include the following:

  • Does a coronary artery pass between the aorta and pulmonary artery where it may get pinched?
  • Does a segment tunnel under a myocardial bridge?
  • Which pathway supplies the posterior surface? Is it the right, left circumflex, or both? That is, is it right dominant, left dominant, or cdominant?
  • Does the LAD wrap around the apex to supply the distal diaphragmatic surface?
  • What vessel supplies the AV node? Is its blood supply impaired?
  • If an infarct is present, which is the infarct-related artery?
  • If abnormal wall motion is seen, which branch obstruction accounts for it?
  • Are any bypass-graft vessels present? If so, where do they originate (left internal mammary, saphenous vein graft from anterior aortic root)? Are they long or short, where do they connect, and how (end to side, side to side)?

The caliber of vessels may be estimated by comparing them with the known diameter of the catheter if it appears on the image. The reviewer should take into account the fact that magnifications differ at different distances from the source to the intensifier with x-ray projection angiography.

After describing the anatomy, note the location, percent narrowing, and character of all focal obstructions (stenoses).

  • For each lesion, is it concentric (symmetric) or eccentric (1 sided)?
  • Is it long or short?
  • Does it abut a branch vessel (which may be lost after intervention)?
  • Is it calcified?
  • Is any thrombus demonstrated?
  • Is evidence of intimal tear demonstrated?
  • Is evidence of vessel spasm demonstrated?
  • Is diffuse narrowing demonstrated?

The flow of contrast agent–labeled blood offers useful information. TIMI criteria may be applied to determine whether the distribution of contrast material is TIMI 0 (incomplete, fails to fill branches and distal part of the vessel), TIMI 1 (slow but complete), or TIMI 2 (brisk and complete). When imaging is performed at a rate of 30 frames per second, the number of frames it takes for a vessel to completely fill may be assessed. The normal number is approximately 21 frames. Filling takes longer in patients with disease than in healthy people, not only in the diseased vessel but also in normal vessels.

Consider how findings may affect possible interventions and report them accordingly. Clinically significant narrowing in the left main coronary artery is a medical emergency because of the amount of myocardium at risk. Other patterns of disease can pose similar risk; examples are proximal disease in both the LAD and a dominant right or left circumflex vessel.

  • What is the caliber of distal vessels that may support a bypass graft?
  • Are they calcified?
  • Is any stenosis near a branch point (such that balloon angioplasty of the lesion may obstruct a branch artery)?
  • How long is the left main coronary artery?
  • How much myocardium is at risk?

Examine images for ancillary findings.

  • Which calcifications move with the heart?
  • Is the mitral valve annulus calcified?
  • Is the aortic root or the aortic valve calcified?
  • Are valve rings, bypass vessel rings or clips, stents, sternal wires, or other evidence of prior surgeries noted?
  • If pacer wires are noted, where do they end?
  • Does evidence exist of chamber enlargement, aneurysm, cardiac displacement, abnormal pulmonary venous return, unusual persistence of fetal structures, or other variants?

If left ventriculography is performed, examine LV function for the EF, regional wall-motion abnormalities, and valve integrity. Hypokinesis indicates educed motion, akinesis indicates no motion, and dyskinesis indicates reversed motion, such as ballooning outward during systole. Note any leakage of contrast material back into the left atrium and any restriction of the valve leaflets.

At the time of coronary angiography, the same set of tools can be used to examine other vessels (eg, renal and carotid arteries). [17]

Degree of confidence

Coronary angiography is the standard for identifying the coronary anatomy and stenoses. In select cases, alternative imaging may appear superior, but be careful to distinguish between high-quality or good-looking pictures and the reliability of the results. Coronary angiography may provide a false-negative result if a branch vessel is occluded at its origin, if the disease is asymmetrical, or if the lesion is cracked, such that the contrast agent can extend close to the full diameter of the vessel even though the vessel cross-sectional area is severely reduced (eg, a star-shaped lesion).

It is possible to miss a lesion that is hidden behind another vessel, but that problem is generally resolved by angled views and by moving the camera (panning) during image collection. If the significance of an obstruction is unclear by coronary angiography, intravascular ultrasound (IVUS) or a flow wire may be used to clarify its spatial extent in relation to the vessel lumen or its impact on flow down a particular branch vessel. A vasodilator may be delivered to assess flow reserve. X-ray angiography is not a good detector of small vessel disease, epitomized by cardiac syndrome-X.

Stress ECG predictive accuracy can be as low as 50%, but it rises above 75% if combined with proBNP blood testing. [9] Stress imaging accuracy for detection of coronary artery disease (CAD) ranges from 70-90% if the target stress level is achieved while off antianginal medications.

Treadmill or bicycle stress testing is generally preferred, followed by dobutamine stress testing, then adenosine combined with low level exercise. Adenosine or dipyridamole alone is less reliable. Chest pain during a dipyridamole stress test is not uncommon in the absence of CAD. [18] Target heart rate (peak HR) for exercise or dobutamine stress testing is 85% of the age-predicted maximum (85% of peak systolic BP × peak HR). Animal studies have shown that the rate-pressure product is a better predictor of the stress levels that should induce detectible ischemia. A 50% blockage should be detected with more than 50% confidence above a rate-pressure product of 20 kilotorr/min and with more than 85% confidence above 25 kilotorr/min.

Limitations

Balloon angioplasty can disrupt an obstruction so that the vessel appears to recover its full diameter when, in fact, the cross-sectional area is improved only minimally and insufficiently. 3D imaging can be used to examine contrast-agent attenuation and the percentage narrowing. On occasion, this condition may be identified by looking at the lesion on different views or by performing IVUS or optical CT.

The introduction of a catheter or a wire can cause intimal dissection (a tear in the lining of a vessel), which may be mistaken for vascular spasm, thrombosis, or a long stenosis on cursory examination. A tissue flap in the endothelial lining may alternate between an open position and an obstructive one, mimicking a spasm; however, it is not responsive to nitrates. The distinction may be a matter of life or death. If clinically significant, stent placement, bypass, placement of a perfusion catheter, or other emergency treatment is typically required to treat a dissection. Sudden obstruction due to a dissection can be deadly, and it does not respond to medications.

Myocardial bridges, or small bands of muscle overlying a vessel, may be mistaken for stenoses; however, these are not amenable to angioplasty. The obstruction from a myocardial bridge is smooth and eccentric. Observation throughout the cardiac cycle shows that the obstruction occurs during systole.

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Computed Tomography

CT imaging of the coronary arteries is achievable with fast CT and EBT systems triggered or gated by ECG to accumulate data when the heart is in diastole. 64-section multidetector-row CT is the newest technology. [19, 20, 21, 22, 16]

With a section thickness of 1 or 0.5 mm or less, the coronary anatomy is laid out in a 3D volume. Image processing can greatly facilitate visualization of the course of vessels and branches and the presence and degree of stenoses. The coronary-artery tree may be viewed as a solid rendering of the surface of the heart, but portions may be obstructed from view.

Proper viewing of each coronary-artery branch should include clean views in which the LV blood pool, aortic root, and all extracardiac structures are removed, and vascular projections are limited to the zones that include the vessel of interest and a margin for partial-volume effects.

Do not rely on threshold-based renderings, which can cause false-stenosis and false-obstruction and which can cause an intravascular thrombus to be missed. The use of a pair of volumes before and after the administration of contrast material for elastic matching [23] greatly facilitates the evaluation by automatically isolating the coronary tree without thresholding. [10]

CT also enables superb evaluation of blood delivery. In principle, CT combined with catheterization permits accurate definition of the extent of collateral-dependent myocardium. [10] (See the CT image below.)

Elastic-match imaging automatically identifies dif Elastic-match imaging automatically identifies differences between image volumes. The acquisition of 1 set of contrast-enhanced chest CT images via the coronaries and a nonenhanced set provides a 3-dimensional view of the coronary-artery tree. The nonenhanced volume data were rendered as holographic projections to provide the anatomic context, and the elastic-match coronary tree was overlaid. In addition to automation, this method avoids thresholding so that small branches and filling defects, if present, are represented properly.

Pizzuto et al found that transthoracic Doppler echocardiography can improve the diagnostic accuracy of multidetector computed tomography (MDCT) for detecting left anterior descending (LAD) coronary artery stenosis. In 144 consecutive patients, coronary anatomy was assessed with MDCT, and echocardiography was used to calculate coronary flow reserve (CFR), by measuring the ratio of hyperemic to baseline peak flow velocity; results of both methods were verified with invasive coronary angiography. [24]

In a univariate model, the prediction of significant LAD stenosis was slightly, but significantly, better with coronary flow reserve (sensitivity 90%, specificity 96%, positive predictive value 84%, negative predictive value 97%, diagnostic accuracy 94%) than with MDCT (sensitivity 80%, specificity 93%, positive predictive value 71%, negative predictive value 95%, diagnostic accuracy 90%). [24]

When the findings from transthoracic Doppler echocardiography and MDCT agreed, the diagnostic accuracy increased (96%). In the 13 patients missed by MDCT, transthoracic Doppler echocardiography proved 100% accurate at predicting significant LAD stenosis. [24]

In a study of myocardial CT perfusion imaging versus single photon emission CT (SPECT) perfusion imaging in the diagnosis of CAD, overall performance was higher for myocardial CT perfusion imaging. Sensitivity and specificity for CT perfusion imaging for diagnosis of CAD were 88% and 55%, respectively, versus 62% and 67% for SPECT. Sensitivities for left main, three-vessel, two-vessel, and one-vessel disease were 92%, 92%, 89%, and 83%, respectively, for CT perfusion imaging and 75%, 79%, 68%, and 41%, respectively, for SPECT. [25]

Degree of confidence

The ability of MRI and CT to depict the anatomy and the absence of notable obstructions is improving rapidly, but it is not uniform. The value of MRI and CT must be assessed in a truly double-blind fashion for each center until standardized, reliable methods are widely established.

Whether MRI and CT results match in terms of the percentage of stenosis is relatively unimportant. Most important is whether MRI and CT reliably depict normal tissue and culprit lesions and, then, whether they establish the severity and the territories supplied by the culprit vessel. Both MRI and CT offer the significant advantage of direct assessment of the zones of impaired blood delivery.

Limitations

MRI shows calcifications as black or signal voids, whereas CT shows calcifications as white and similar to contrast-filled blood. These appearances can influence the estimation of stenoses.

Heavy calcification causes a beam-hardening artifact on CT that can interfere with visualization. Stents cause a local disturbance stronger on MRI than on CT. Also, with 3D MRI or CT, be certain to understand how the images account for local curvature in and out of the imaging planes. In finding the best plane to show a vessel, radiologists can mistake a local curve that is out of plane for an apparent stenosis. Proper image processing resolves this problem.

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Magnetic Resonance Imaging

Coronary MRI has improved from the early methods [3] and equipment sufficient to identify normal proximal coronary arteries and courses, but it is not a clinical replacement for coronary angiography apart from ruling out aberrant coronary origins, demonstrating graft or native vessel patency, or follow-up on specific lesions.

Coronary MRI may be performed by using a 3D volume, but the trade-off in time and resolution favors imaging in selective planes that address each branch of interest. As a 3D volume, MRIs may show the coronary tree in a way similar to the methods described for CT. Background tissue may be suppressed with fat saturation, tissue saturation, magnetization transfer, and/or T2 preparation (90°-180°-180°- ... -180°-90°). [26]

The vessel-plane approach is as follows: Any desired target plane can be obtained by specifying 3 points to include in the plane, by drawing the lines of intersection with 2 previous images at different angles, or (commonly) by drawing a single line of intersection with a previous image that is perpendicular to the desired view. For example, to obtain a short-axis view of the coronary sinus, first obtain a long-axis view of the LV parallel to the septum and perpendicular to the AV groove, then prescribe a plane in the AV groove perpendicular to that view passing through the 2 observed points of intersection on the first view with the coronary sinus, seen as bright dots anterior and posterior to the mitral valve.

Other points regarding MRI to evaluate CAD are the following:

  • A transverse stack of images covering the aortic root depicts the origin of the RCA and the left main coronary artery. The typical section thickness should be 3 mm or less. A bright- or dark-blood technique can be applied with the use of single frames or with a dynamic movie series.
  • An additional distal transverse image shows a cross-section of the RCA, LAD, and LCX.
  • From 2 points along the proximal vessel and from 1 point from the distal vessel, a plane that captures the desired segment is selected. The plane may be adjusted to be thick enough to encompass out-of-plane bends. As an alternative, it may be subdivided into a stack of thin imaging planes for a localized 3D stack of images.
  • The course of the RCA in the AV groove can quickly be ascertained from a 4-chamber long-axis view of the heart by obtaining 1 preliminary image perpendicular to the AV groove and parallel to the septum through the mid RV. This provides 2 points of intersection with the RCA: 1 anterior and 1 posterior in the AV groove. Prescribing a plane through those 2 points from the long axis image gives the desired view.
  • The posterior descending artery requires a different imaging plane, as do the LAD, LCX, and major branches. The course of the LCX in the AV groove is assessed in a way similar to that used for imaging the RCA, by acquiring a scout image parallel to the septum to identify 2 points to include in one final short-axis image. However, in this case, the scout image should be laterally displaced to the outer third, because the distal LCX is often hard to identify.
  • The authors routinely identify the proximal course of the coronary arteries in young patients who have had syncope to look for aberrant origins. A complete absence of abnormalities suggests a good prognosis.
  • MRI with contrast is an excellent method to identify myocardial scar (infarction) as small as 1% of the myocardium, which is a very strong prognostic factor [27] , while also assessing perfusion and precise function of left and right ventricles. It can also be combined with stress testing and coronary imaging for a "one stop shop."
  • MRI is the preferred test for right ventricular injury or infarction.
  • Apparent stenosis must be distinguished from an out-of-plane bend.
  • A signal void from flow disturbance may exaggerate apparent stenosis.
  • MRI is well established as a means to assess the patency of a bypass graft.

According to one study, infarct tissue heterogeneity that is identified by cardiac magnetic resonance imaging is associated with mortality beyond that of left ventricular ejection fraction in patients who have both coronary artery disease and left ventricular dysfunction. It was found that this is particularly true in patients with mild or moderate left ventricular dysfunction. The authors suggested that further studies incorporating cardiac magnetic resonance imaging in clinical decision-making for defibrillator therapy are warranted. [28]

Degree of confidence

According to one study, infarct heterogeneity identified by cardiac magnetic resonance imaging is associated with mortality beyond left ventricular ejection fraction (LVEF) in patients with coronary artery disease and left ventricular dysfunction. It was found that this is particularly true in patients with mild or moderate left ventricular dysfunction. The authors suggested that further studies incorporating cardiac magnetic resonance imaging in clinical decision-making for defibrillator therapy are warranted.

MRI offers high sensitivity to changes in wall function, eg, wall thickening and radial motion. [11] MRI may be useful in identifying and quantifying impaired blood delivery and wall function in response to interventions. [7, 29, 30, 31, 32, 33, 34, 35] Such applications are perhaps more vital than visualizing the percentage of stenosis.

Confidence in the data depends on the speed and quality of the imaging method, the cooperation of the patient (shallow regular breathing or several matching breath holds), the accuracy of ECG triggering or gating, and the anatomic knowledge and judgment of the person directly supervising data collection.

Usual ECG signal in MRI is markedly distorted by competing signals from movement in a magnetic field and by moving magnetic fields, particularly from blood flow in the great vessels, called the magnetohydrodynamic effect. That distortion makes it difficult to perform electrographic safety monitoring for ischemic changes.

Cardiac MRI with the vessel-chasing approach requires highly informed decision making as the data are being acquired. If the operator acquiring the data understands what the coronary angiogram demonstrates, the views may be manipulated for the best match. This consideration is not necessarily positive, because the operator may exaggerate the agreement.

The ability of MRI and CT to identify anatomy and the absence of clinically significant obstructions is improving rapidly, but it is not uniform. The value of MRI and CT must be assessed in a truly double-blind fashion for each center until standardized and reliable methods are widely established.

Whether MRI and CT results match in terms of the percentage of stenosis is relatively unimportant. Most important is whether MRI and CT reliably depict normal tissue and culprit lesions and, then, whether they help in establishing their severity and in depicting the territories supplied by the culprit vessel. Both MRI and CT offer the notable advantage of enabling direct assessment of the zones with impaired blood delivery.

Limitations

In an apparent stenosis, be certain that it is not a partial-volume artifact or a velocity-shear effect. Because local differences in velocity can cause a signal void, estimates of stenosis may be exaggerated.

Magnetic susceptibility artifacts may produce signal voids. Stents, clips, and wires cause local disturbances.

The presence of pacemaker wire is considered a relative contraindication to MRI because the rapidly changing magnetic fields may induce a voltage that can trigger an arrhythmia, induce a burn, or shorten the battery life.

Also, when the patient enters and leaves the magnet, the magnetic reed switch on most pacemakers will switch it to fixed mode, and the temperature may rise in metal devices. For example, a pacemaker generator may warm by 1-2°C. However, with informed consent, careful pulse monitoring, and a readiness to promptly abort a pulse sequence if an arrhythmia is induced, patients with pacers have undergone MRI with no apparent consequence and no change in their pacer thresholds. In the dozen reports of mishaps related to pacemakers and MRI, none were caused by MRI.

On MRIs, calcification is depicted as a black area or signal void, whereas CT shows calcifications as white, similar to blood filled with contrast agent. These appearances can influence the estimation of stenoses. Also, with 3D MRI or CT, be certain to understand how the images account for local curvature in and out of the imaging planes. In finding a best MRI plane for showing a vessel, radiologists can mistake a local curve that is out of plane for an apparent stenosis. Proper image processing resolves this problem.

With MRI, flow disturbances that cause velocity shear (range of phases in each picture element or pixel resulting from different rates of motion of blood) cause a local decrease in signal intensity, which may create or exaggerate an apparent stenosis.

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Ultrasonography

Echocardiography can be used to identify the left main coronary artery. In some patients, much of the RCA and LAD can be viewed; however, in most patients, the imaging window is inadequate for useful coronary imaging from outside the chest.

In the catheterization laboratory, IVUS may be performed to examine the coronary arteries from the inside and to characterize plaque. However, the diameter of the device limits the ability to pass through tight stenoses. Also, the injection of a sonographic contrast agent (eg, agitated Renografin) into the coronary arteries, combined with transthoracic or esophageal ultrasonography, can be useful in identifying perfusion territories.

Pizzuto et al found that transthoracic Doppler echocardiography can improve the diagnostic accuracy of multidetector computed tomography (MDCT) for detecting left anterior descending (LAD) coronary artery stenosis. In 144 consecutive patients, coronary anatomy was assessed with MDCT, and echocardiography was used to calculate coronary flow reserve (CFR), by measuring the ratio of hyperemic to baseline peak flow velocity; results of both methods were verified with invasive coronary angiography.

In a univariate model, the prediction of significant LAD stenosis was slightly, but significantly, better with coronary flow reserve (sensitivity 90%, specificity 96%, positive predictive value 84%, negative predictive value 97%, diagnostic accuracy 94%) than with MDCT (sensitivity 80%, specificity 93%, positive predictive value 71%, negative predictive value 95%, diagnostic accuracy 90%). When the findings from transthoracic Doppler echocardiography and MDCT agreed, the diagnostic accuracy increased (96%). In the 13 patients missed by MDCT, transthoracic Doppler echocardiography proved 100% accurate at predicting significant LAD stenosis. [24]

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Nuclear Imaging

Nuclear medicine study does not depict the coronary arteries, but it does demonstrate various metabolites useful in identifying perfusion defects and tissue viability. Thallium-201 and technetium-99m sestamibi are widely used and may be combined to shorten the study of myocardial uptake of radioactive tracer at rest and during stress. [36]

Although a rest-and-stress thallium study takes more than 4 hours, a combined study performed with thallium and sestamibi may be completed in less than 2 hours.

By using PET, a rest-and-stress study with rubidium-82 may be completed in 30 minutes, because the agent has a half-life of less than 5 minutes. A defect during stress that is not evident at rest indicates a zone of induced ischemia. A defect at rest and also during stress indicates persisting metabolic dysfunction, either from infarction (scar) or hibernation (prolonged dysfunction). PET with ammonia, fluorinated glucose, or other agents may be used to determine if the tissue with a defect at rest is viable. [36]

Degree of confidence

Nuclear medicine tests for CAD improve the predictive accuracy over that of stress tests alone, to approximately 90%. The utility of these tests depends on the previous probability of disease and on whether they are being used to identify CAD or to clarify the pathophysiology of known disease.

Limitations

Breast attenuation may cause an apparent defect on radionuclide images. Attenuation correction and multiplanar imaging mitigate the problem.

Unusual motion, such as that from a bundle branch block or coughing during imaging, may cause false-positive results. A persisting defect is commonly interpreted as a fixed defect or a scar, but it may represent prolonged yet still-reversible ischemic impairment of tracer uptake.

The low resolution of nuclear medicine studies compared with that of other modalities may result in false-negative results. Also, global disease may be missed because defects are generally identified by comparing them to regions with high uptake of the tracer.

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